Treatment With Adalimumab 80 mg Every Other Week in Inflammatory Bowel Disease: Results of Treatment Intensification in Clinical Practice.

Background: Loss of response to anti-tumor necrosis factor drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic, or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40 mg every week (ew). Availability of ADA 80 mg prefilled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80 mg eow. Methods: This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80 mg eow with clinical, biomarker, and drug-level assessments were included. Demographics and clinical, biological, and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results: Eighty-seven patients (72 Crohn's disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels-<5 µg mL-1-(17%), low ADA levels-<5 µg mL-1-without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, magnetic resonance imaging, capsule endoscopy, and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80 mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalization of biomarkers). After a median follow-up of 19 months (interquartile range 13-25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalizations, or deaths. Drug costs did not increase with the 80 mg eow regimen versus a standard intensification regimen. Conclusions: ADA intensification to 80 mg eow was safe, effective, and did not increase drug costs versus standard intensification to 40 mg ew in our experience.

Faecal Microbiota Transplantation is a simple, effective and safe treatment in the management of C. difficile infection in daily clinical practice.

INTRODUCTION: Faecal microbiota transplantation (FMT) is a treatment supported by wide scientific evidence and proved to be very effective in the management of Clostridioides difficile infection (CDI). The objective of this study is to analyze its effectiveness and safety in a real clinical practice setting. METHODS: Retrospective, single-center and descriptive observational study in which all FMT performed between May 2016 and December 2020 were included. Technical success was defined as the successful administration of the faecal preparation in the patient's gastrointestinal tract and clinical success the disappearance of diarrhoea in the first 72 h after the procedure with no relapse within the following 8 weeks after the therapy was started. RESULTS: 15 FMT were performed in 13 patients. Median age was 79 years (range: 40-98 years); being 60% women and 33.3% depedent persons. The indication for FMT was recurrent CDI in 84.6%. All FMTs were performed by colonoscopy and from related donors. With a first procedure, the FMT was effective in 11 of 13 patients (84.61%; 95% CI; 54.55-98.07). Time until resolution of symptoms was less than 48 h in all cases. Post-transplant follow-up was 25.66 ±â€¯17.5 months. No significant short or long-term complications were recorded at follow-up. CONCLUSION: TMF is a simple, effective and safe procedure in CD infection, even in elderly patients or those with great comorbidities.

Comparison of small-bowel colon capsule endoscopy system to conventional colonoscopy for the evaluation of ulcerative colitis activity.

Background and aims Diagnosis and monitoring of ulcerative colitis (UC) includes conventional colonoscopy. This procedure is invasive and does not exclude small-bowel Crohn's disease (CD). Current therapeutic goals include mucosal healing which may lead to an increased number of endoscopic procedures in many patients. The small-bowel colon capsule endoscopy (SBC-CE) system visualizes the small bowel and colon. The aim of this study was to evaluate the performance and adverse events of SBC-CE in patients with UC. Methods This was a prospective, feasibility study involving two study sites. Patients with active UC underwent SBC-CE and colonoscopy. Kappa statistics were performed to assess the agreement between SBC-CE and colonoscopy. Adverse events (AEs) data were collected throughout and following the procedure. Results In total, 30 consecutive patients were recruited, and 23 of those were included in the final analysis. For the primary end point, evaluation of the extent of UC disease in the colon, the percent agreement between SBC-CE and colonoscopy was moderate (56.5 %); kappa coefficient 0.42. The percent agreement between SBC-CE and colonoscopy for UC disease activity, based on Mayo endoscopic sub-score, was 95.7 %; kappa coefficient 0.86. Disease activity in the more proximal small bowel was detected in two patients with SBC-CE. No SBC-CE device-related AEs were reported. Conclusions When comparing SBC-CE to conventional colonoscopy, there was a moderate agreement for the extent of UC disease and a very good overall agreement between the two modalities for UC disease activity.

Usefulness of Thiopurine Monotherapy for Crohn's Disease in the Era of Biologics: A Long-Term Single-Center Experience.

BACKGROUND: Thiopurines are classically used in Crohn's disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage. AIM: To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics. METHODS: The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added. RESULTS: A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17-84) years. Median follow-up was 43 (range 0.2-289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105-147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990-1995 (4.7% of all TF); 8 in 1996-2000 (5.4%); 22 in 2001-2005(15%); 41 in 2006-2010 (28%); 69 in 2011-2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p < 0.05). Seventy-four patients (18.4%) stopped AZA due to AE, and 73(19%) due to lack of efficacy. Regarding AZA indication, prevention of postoperative recurrence obtained better results than steroid dependency (p = 0.001); perianal fistulizing CD predicted poorer outcomes (p = 0.002). CONCLUSION: An important proportion of CD patients under AZA monotherapy experienced TF in our experience. Although AZA monotherapy remains useful for CD in the era of biologics, current clinical practice is shifting to anti-TNFα biologic drugs in an increasing proportion of patients.

Idiopathic portal hypertension regarding thiopurine treatment in patients with inflammatory bowel disease.

INTRODUCTION: The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown. MATERIAL AND METHODS: A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment. RESULTS: At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn's disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy-five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3). CONCLUSION: Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage.

Hipertensión portal idiopática secundaria a tratamiento tiopurínico en pacientes con enfermedad inflamatoria intestinal / Idiopathic portal hypertension regarding thiopurine treatment in patients with inflammatory bowel disease

Introducción: entre los efectos adversos hepáticos secundarios al tratamiento tiopurínico en pacientes con enfermedad inflamatoria intestinal (EII), se ha descrito la posibilidad de desarrollar hipertensión portal idiopática. Esta patología de etiología y prevalencia real inciertas puede comprometer el pronóstico de estos pacientes, por lo que se debe tener un alto grado de sospecha para su diagnóstico precoz. Material y métodos: se ha llevado a cabo un estudio transversal en una cohorte de pacientes con EII en seguimiento en nuestra unidad para determinar la prevalencia del diagnóstico de HTP idiopática (HTPI) y su relación con el tratamiento tiopurínico. Resultados: en nuestro centro, en el momento del análisis había 1.419 pacientes en seguimiento por enfermedad inflamatoria intestinal. De estos, 927 pacientes se encuentran bajo tratamiento con fármacos tiopurínicos (o lo han estado durante la evolución de su enfermedad), lo que supone el 65,3% de la población: 689 pacientes con azatioprina (74,3%) y 238 con 6-mercaptopurina (25,7%). En total, se identificaron 4 pacientes con EII tipo enfermedad de Crohn con hipertensión portal idiopática en probable relación con el tratamiento tiopurínico, lo que supuso un 4,3% del total, es decir, una incidencia de 4,3 casos por cada 1.000 pacientes con EII tratados con tiopurínicos. Las características basales de los pacientes se describen en la tabla I. El 75% de los pacientes debutó con signos o síntomas de hipertensión portal: 1 paciente con encefalopatía hepática y 2 pacientes con hemorragia digestiva por varices esofágicas. Solo un paciente se encontraba asintomático, pero se sospechó el diagnóstico de HTP por trombopenia aislada. No obstante, cabe destacar que todos los pacientes presentaban trombopenia previamente aunque no se había sospechado el diagnóstico de HTP a pesar de un exhaustivo estudio. A todos los se realizó ecografía abdominal con fibroscan, cateterismo de venas suprahepáticas, así como biopsia hepática como parte del estudio etiológico de hipertensión portal. En la ecografía abdominal se objetivaron datos indirectos de HTP en todos los pacientes (como esplenomegalia), descartándose asimismo cirrosis hepática. El fibroscan mostraba datos de fibrosis hepática significativa (F2-F3). Además, a todos los pacientes se les realizó una angiorresonancia en la que se descartó trombosis del eje esplenoportal como causa de HTP. Por último, la anatomía patológica de la biopsia hepática descartó la presencia de cirrosis hepática, apoyando el diagnóstico de HTP idiopática (Tabla II). Conclusiones: la hipertensión portal idiopática secundaria a tratamiento tiopurínico en pacientes con enfermedad inflamatoria intestinal es un fenómeno poco frecuente, pero ha de ser tenido en cuenta en el diagnóstico diferencial para un diagnóstico precoz, principalmente en pacientes con tratamiento tiopurínico de larga evolución. La presencia de trombopenia es a menudo el único factor predictor de su desarrollo en fases preclínicas (AU)

Introduction: The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown. Material and methods: A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment. Results: At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn’s disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy-five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3). Conclusion: Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage (AU)